EP2721026B1 - Phosphatester von gyrase und topoisomeraseinhibitoren - Google Patents

Phosphatester von gyrase und topoisomeraseinhibitoren Download PDF

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EP2721026B1
EP2721026B1 EP12731853.3A EP12731853A EP2721026B1 EP 2721026 B1 EP2721026 B1 EP 2721026B1 EP 12731853 A EP12731853 A EP 12731853A EP 2721026 B1 EP2721026 B1 EP 2721026B1
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infections
compound
resistant
fluoro
tetrahydrofuran
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EP2721026A1 (de
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Youssef Laafiret BENNANI
Paul S. Charifson
Anne-Laure Grillot
Arnaud Letiran
Hardwin O'dowd
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Vertex Pharmaceuticals Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C07F9/65586—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system at least one of the hetero rings does not contain nitrogen as ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
    • A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
    • A61K31/688—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols both hydroxy compounds having nitrogen atoms, e.g. sphingomyelins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/16—Otologicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/05—Isotopically modified compounds, e.g. labelled

Definitions

  • the present invention relates to compounds for use in a method of controlling, treating or reducing the advancement, severity or effects of a bacterial infection in a patient, comprising administering to said patient a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof.
  • the instant compounds are prodrugs of their parent compound, ( R )-1-ethyl-3-(6-fluoro-5-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-7-(tetrahydrofuran-2-yl)-1H-benzo[d]imidazol-2-yl)urea.
  • the activity exhibited upon administration of the prodrug is principally due to the presence of the parent compound that results from cleavage of the prodrug.
  • the bacterial infection is characterized by the presence of one or more of Streptococcus pneumoniae, Enterococcus faecalis, or Staphylococcus aureus.
  • the compounds of formula (I) may also be co-administered with other antibiotics to increase the effect of therapy or prophylaxis against various bacterial infections.
  • the compounds of this invention are administered in combination therapies with other agents, they may be administered sequentially or concurrently to the patient.
  • pharmaceutical or prophylactic compositions according to this invention comprise a combination of a compound of formula (I) and another therapeutic or prophylactic agent.
  • the composition including a solid form of a formula (I) compound is administered orally, and the additional antibiotic agent, for example, a natural penicillin, a penicillinase-resistant penicillin, an antipseudomonal penicillin, an aminopenicillin, a first generation cephalosporin, a second generation cephalosporin, a third generation cephalosporin, a fourth generation cephalosporin, a carbapenem, a cephamycin, a monobactam, a quinolone, a fluoroquinolone, an aminoglycoside, a macrolide, a ketolide, a polymyxin, tetracycline or a sulfonamide is administered orally.
  • the additional therapeutic agent is administered iv.
  • the implantable or indwelling device coating can include a blend of polymers each having a different release rate of the therapeutic agent.
  • the coating can include a polylactic acid/polyethylene oxide (PLA-PEO) copolymer and a polylactic acid/polycaprolactone (PLA-PCL) copolymer.
  • the polylactic acid/polyethylene oxide (PLA-PEO) copolymer can exhibit a higher release rate of therapeutic agent relative to the polylactic acid/polycaprolactone (PLA-PCL) copolymer.
  • the relative amounts and dosage rates of therapeutic agent delivered over time can be controlled by controlling the relative amounts of the faster releasing polymers relative to the slower releasing polymers.
  • the pharmaceutical compositions of this invention will be administered from about 1 to 5 times per day or alternatively, as a continuous infusion.
  • the compositions of the present invention may be administered in a pulsatile formulation.
  • Such administration can be used as a chronic or acute therapy.
  • the amount of active ingredient that may be combined with the carrier materials to produce a single dosage form will vary depending upon the host treated and the particular mode of administration.
  • a typical preparation will contain from about 5% to about 95% active compound (w/w).
  • such preparations contain from about 20% to about 80% active compound.
  • the ( R )-1-ethyl-3-(6-fluoro-5-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-7-(tetrahydrofuran-2-yl)-1H-benzo[d]imidazol-2-yl)urea 23 may then be converted to the phosphate or phosphate salt prodrugs according to Scheme 1 below.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Cardiology (AREA)
  • Rheumatology (AREA)
  • Dermatology (AREA)
  • Pain & Pain Management (AREA)
  • Ophthalmology & Optometry (AREA)
  • Urology & Nephrology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Endocrinology (AREA)
  • Reproductive Health (AREA)
  • Pulmonology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Claims (15)

  1. Verbindung der Formel (I):
    Figure imgb0022
     oder ein pharmazeutisch annehmbares Salz davon, worin
    X für -PO(OH)O-R1 oder -PO(O-M+)O-R1 steht;
    M+ ein pharmazeutisch annehmbares monovalentes Kation darstellt;
    R1 für (C1-C20)-Alkyl, (C2-C20)-Alkenyl, -(CH2CH20)nCH3 oder R2 steht; worin besagtes Alkyl oder Alkenyl gegebenenfalls substituiert ist mit R2, -OR9, -N(R9)2, -CN, -C(O)OR9, -C(O)N(R9)2,-N(R9)-C(O)-R9, Halogen, -CF3 oder -NO2;
    jedes R2 unabhängig ein 5-6-gliedriges carbocyclisches oder heterocyclisches aliphatisches Ringsystem darstellt; worin jedes der besagte heterocyclischen Ringsysteme ein oder mehrere Heteroatome enthält, ausgewählt aus O, N und N(R9); und worin jedes der besagten Ringsysteme gegebenenfalls 1 bis 4 Substituenten enthält, unabhängig ausgewählt aus -OH, C1-C4-Alkyl und -O-(C1-C4)-Alkyl;
    jedes R9 unabhängig für H oder eine C1-C4-Alkylgruppe steht; und
    n eine ganze Zahl 1 bis 5 ist.
  2. Verbindung nach Anspruch 1, worin X für -PO(O-M+)O-R1 steht; und M+ ausgewählt ist aus einer Gruppe bestehend aus Li+, Na+, K+, N-Methyl-D-glucamin und N(R9)4 +.
  3. Verbindung nach jedem Anspruch 1, worin R1 für (C1-C20)-Alkyl, (C2-C20)-Alkenyl oder-O(CH2CH2O)nCH3, worin n eine ganze Zahl 1, 2 oder 3 ist, Morpholinoethyl, 4-Ethyltetrahydro-2H-pyranyl, Piperidinylethyl, Piperazinylethyl oder Pyrrolidinylethyl steht.
  4. Verbindung nach Anspruch 3, worin R1 für Morpholinoethyl, 4-Ethyltetrahydro-2H-pyranyl, Piperidinylethyl, Piperazinylethyl oder Pyrrolidinylethyl steht.
  5. Verbindung nach Anspruch 3, worin R1 für (C1-C20)-Alkyl steht.
  6. Verbindung nach Anspruch 3, worin R1 für -O(CH2CH2O)nCH3 steht, worin n eine ganze Zahl 1, 2 oder 3 ist.
  7. Verbindung nach Anspruch 1, worin die Verbindung ausgewählt ist aus der Gruppe bestehend aus (R)-2-(5-(2-(3-Ethylureido)-6-fluor-7-(tetrahydrofuran-2-yl)-1H-benzo[d]imidazol-5-yl)pyrimidin-2-yl)propan-2-yl-2-(2-Methoxyethoxy)ethyl-hydrogenphosphat, Ammonium-(R)-2-(5-(2-(3-ethylureido)-6-fluor-7-(tetrahydrofuran-2-yl)-1H-benzo[d]imidazol-5-yl)pyrimidin-2-yl)propan-2-yl-2-(2-Methoxyethoxy)ethylphosphat, (R)-2-(5-(2-(3-Ethylureido)-6-fluor-7-(tetrahydrofuran-2-yl)-1H-benzo[d]imidazol-5-yl)pyrimidin-2-yl)propan-2-yl-Hexadecylhydrogenphosphat, Ammonium-(R)-2-(5-(2-(3-ethylureido)-6-fluor-7-(tetrahydrofuran-2-yl)-1H-benzo[d]imidazol-5-yl)pyrimidin-2-yl)propan-2-yl-Hexadecylphosphat und 2-(5-(2-(3-Ethylureido)-6-fluor-7-((R)-tetrahydrofuran-2-yl)-1H-benzo[d]imidazol-5-yl)pyrimidin-2-yl)propan-2-yl-2-morpholinoethyl-hydrogenphosphat.
  8. Pharmazeutische Zusammensetzung, welche eine Verbindung gemäß einem der Ansprüche 1-7 oder ein pharmazeutisch annehmbares Salz davon und einen pharmazeutisch annehmbaren Träger, Adjuvans oder Vehikel umfasst.
  9. Pharmazeutische Zusammensetzung nach Anspruch 8, welche ferner ein zweites therapeutisches Agens umfasst, ausgewählt aus einem Antibiotikum, einem entzündungshemmenden Mittel, einem Matrix-Metalloprotease-Inhibitor, einem Lipoxygenase-Inhibitor, einem Cytokin-Antagonisten, einem Immunsuppressivum, einem Anti-Krebsmittel, einem Anti-Virusmittel, einem Zytokin, einem Wachstumsfaktor, einem Immunmodulator, einem Prostaglandin oder einer anti-vaskulären Hyperproliferationsverbindung.
  10. Pharmazeutische Zusammensetzung nach Anspruch 8, welche ferne ein Agens umfasst, das die Anfälligkeit von bakteriellen Organismen für Antibiotika erhöht.
  11. Verbindung gemäß einem der Ansprüche 1-7 zur Verwendung beim Verringern oder Hemmen von Streptococcus pneumoniae, Staphylococcus epidermidis, Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Clostridium dif ficile, Moraxella catarrhalis, Neisseriagonorrhocae, Neisseria meningitidis, Mycobacterium tuberculosis, Mycobacterium avium Komplex, Mycobacterium abscessus, Mycobacterium kansasii, Mycobacterium ulcerans, Chlamydophilapneumoniae, Chlamydia trachomatis, Haemophilus influenzae, Streptococcuspyogenes oder β-hämolytischer bakterieller Streptokokken-Menge in einer biologischen Probe.
  12. Verbindung gemäß einem der Ansprüche 1-7 zur Verwendung beim Kontrollieren, Behandeln oder Verringern des Voranschreitens, der Schwere oder Wirkungen einer nosokomialen oder einer nicht-nosokomialen bakteriellen Infektion in einem Patienten.
  13. Verbindung zur Verwendung gemäß Anspruch 12, wobei die bakterielle Infektion gekennzeichnet ist durch die Anwesenheit von einem oder mehreren von Streptococcus pneumoniae, Staphylococcus epidermidis, Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Clostridium dif ficile, Moraxella catarrhalis, Neisseriagonorrhocae, Neisseria meningitidis, Mycobacterium tuberculosis, Mycobacterium avium Komplex, Mycobacterium abscessus, Mycobacterium kansasii, Mycobacterium ulcerans, Chlamydophilapneumoniae, Chlamydia trachomatis, Haemophilus influenzae, Streptococcuspyogenes oder β-hämolytischen Streptokokken, gegebenenfalls worin die bakterielle Infektion ausgewählt ist aus einem oder mehreren der folgenden: Infektionen der oberen Atemwege, Infektionen der unteren Atemwege, Ohreninfektionen, pleuropulmonale und bronchiale Infektionen, komplizierte Harnwegsinfektionen, unkomplizierte Harnwegsinfektionen, intra-abdominale Infektionen, kardiovaskuläre Infektionen, einer Blutstrominfektion, Sepsis, Bakteriämie, ZNS-Infektionen, Haut- und Weichgewebeinfektionen, GI-Infektionen, Knochen- und Gelenkinfektionen, Genitalinfektionen, Augeninfektionen oder granulomatöse Infektionen, unkomplizierten Haut- und Hautstrukturinfektionen, komplizierten Haut-und Hautstrukturinfektionen (cSSSI), Katheterinfektionen, Pharyngitis, Sinusitis, Otitis externa, Otitis media, Bronchitis, Empyem, Pneumonie, ambulant erworbenen Pneumonien (CAP), hospitalisiert erworbener Pneumonie, hospitalisierter bakterieller Pneumonie, Diabetesfuß-Infektionen, Vancomycin-resistenten Enterokokkeninfektionen, Zystitis und Pyelonephritis, Nierensteinen, Prostatitis, Peritonitis und anderen inter-abdominalen Infektionen, Dialyse-assoziierter Peritonitis, viszeralen Abszessen, Endokarditis, Myokarditis, Perikarditis, Transfusion-assoziierter Sepsis, Meningitis, Enzephalitis, Gehirnabszess, Osteomyelitis, Arthritis, Genitalgeschwüren, Urethritis, Vaginitis, Zervicitis, Gingivitis, Konjunktivitis, Keratitis, Endophthalmitisa, einer Infektion bei zystischen Fibrosepatienten oder einer Infektion von febrilen neutropenischen Patienten.
  14. Verbindung zur Verwendung gemäß Anspruch 13, wobei die bakterielle Infektion ausgewählt ist aus einer oder mehreren der folgenden: ambulant erworbenen Pneumonien (CAP), hospitalisiert erworbener Pneumonie, hospitalisierter bakterieller Pneumonie, Bakteriämie, Diabetesfuß-Infektionen, Katheterinfektionen, unkomplizierten Haut- und Hautstrukturinfektionen, komplizierten Haut- und Hautstrukturinfektionen (cSSSI), Vancomycin-resistenten Enterokokkeninfektionen oder Osteomyelitis.
  15. Verbindung gemäß Anspruch 12 zur Verwendung in Kombination mit einem Antibiotikum, einem entzündungshemmenden Agens, einem Matrix-Metalloprotease-Inhibitor, einem Lipoxygenase-Inhibitor, einem Zytokin-Antagonisten, einem Immunsuppressivum, einem Antikrebsmittel, einem Antivirusmittel, einem Zytokin, einem Wachstumsfaktor, einem Immunmodulator, einem Prostaglandin oder einer antivaskulären Hyperproliferationsverbindung, entweder als Teil einer multiplen Dosierungsform zusammen mit besagter Verbindung oder Salz oder als getrennte Dosierungsform.
EP12731853.3A 2011-06-20 2012-06-20 Phosphatester von gyrase und topoisomeraseinhibitoren Active EP2721026B1 (de)

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PCT/US2012/043266 WO2012177707A1 (en) 2011-06-20 2012-06-20 Phosphate esters of gyrase and topoisomerase inhibitors

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JP (1) JP5977344B2 (de)
KR (1) KR101941420B1 (de)
CN (1) CN103702994B (de)
ES (1) ES2576298T3 (de)
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Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2824403C (en) 2011-01-14 2019-09-24 Vertex Pharmaceuticals Incorporated Solid forms of gyrase inhibitor (r)-1-ethyl-3-[6-fluoro-5-[2-(1-hydroxy-1-methyl-ethyl)pyrimidin-5-yl]-7-(tetrahydrofuran-2-yl)-1h-benzimidazol-2-yl]urea
TWI546298B (zh) 2011-01-14 2016-08-21 維泰克斯製藥公司 旋轉酶及拓樸異構酶ｉｖ抑制劑
ES2526902T3 (es) * 2011-01-14 2015-01-16 Vertex Pharmaceuticals Incorporated Procesos de producción de inhibidores de la girasa y topoisomerasa IV
BR112013017977A2 (pt) * 2011-01-14 2019-09-24 Vertex Pharma formas sólidas de inibidor de girase (r) 1-etil-3-[5-[2-{1-hidroxi-1-metil-etil}pirimidin-5-il]-7-(tetrai-drofuran-2-il)-1h-benzimidazol-2-il]ureia
EP2721026B1 (de) * 2011-06-20 2016-03-02 Vertex Pharmaceuticals Incorporated Phosphatester von gyrase und topoisomeraseinhibitoren
US9018216B2 (en) * 2012-07-18 2015-04-28 Vertex Pharmaceuticals Incorporated Solid forms of (R)-2-(5-(2-(3-ethylureido)-6-fluoro-7-(tetrahydrofuran-2-yl)-1H-benzo[d]imidazol-5-yl)pyrimidin-2-yl)propan-2-yl dihydrogen phosphate and salts thereof
US9572809B2 (en) 2012-07-18 2017-02-21 Spero Trinem, Inc. Combination therapy to treat Mycobacterium diseases
MX2016010057A (es) 2014-02-03 2017-04-27 Spero Gyrase Inc Compuestos antibacterianos.
CN107108672B (zh) 2014-10-03 2019-11-08 Ucb生物制药私人有限公司 稠合的五环咪唑衍生物
EP3285874B1 (de) * 2015-04-22 2021-03-17 Matinas BioPharma Nanotechnologies, Inc. Zusammensetzungen und verfahren zur behandlung von mykobakterieninfektionen und lungenerkrankungen
US10654861B2 (en) 2016-04-01 2020-05-19 UCB Biopharma SRL Fused pentacyclic imidazole derivatives as modulators of TNF activity
CA3018992A1 (en) 2016-04-01 2017-10-05 Ucb Biopharma Sprl Fused hexacyclic imidazole derivatives as modulators of tnf activity
CA3018907A1 (en) 2016-04-01 2017-10-05 Ucb Biopharma Sprl Fused pentacyclic imidazole derivatives as modulators of tnf activity
BR112018069936A2 (pt) 2016-04-01 2019-02-05 Sanofi Sa derivados de imidazol pentacíclicos fundidos como moduladores de atividade do tnf
WO2018167176A1 (en) 2017-03-15 2018-09-20 Ucb Biopharma Sprl Fused pentacyclic imidazole derivatives as modulators of tnf activity
CN109725101B (zh) * 2017-10-31 2021-11-19 正大天晴药业集团股份有限公司 盐酸特拉万星原料中有关物质的检测方法
US11793754B1 (en) 2022-06-16 2023-10-24 King Abdulaziz University Sodium hypochlorite and chlorhexidine based nanoemulsions and a method of preparation thereof

Family Cites Families (48)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2015676A1 (de) 1970-04-02 1971-10-21 Farbenfabriken Bayer Ag, 5090 Leverkusen Neue Imine der 2-Formyl-chinoxalindi-N-oxidcarbon-säure-(3) und deren Salze, Verfahren zu ihrer Herstellung und ihre Verwendung als antimikrobielle Mittel
US4174400A (en) 1978-09-13 1979-11-13 Merck & Co., Inc. Anthelmintic benzimidazoles
US4512998A (en) 1980-10-20 1985-04-23 Schering Corporation Anthelmintic benzimidazole carbamates
CA2028530A1 (en) 1989-11-21 1991-05-22 Christian Hubschwerlen Substituted pyrimidobenzimidazole derivatives
DE69430823T2 (de) 1993-09-22 2003-02-20 Xoma Technology Ltd., Berkeley Verfahren zur behandlung von gram-negativen bakterien infektion durch verabreichung von bakterientötendem/durchlässigkeiterhöhendem (bpi) proteinprodukt und antibiotikum
PT754050E (pt) 1994-01-14 2002-11-29 Xoma Technology Ltd Metodos e materiais contra bacterias gram-positivas
DE19514313A1 (de) 1994-08-03 1996-02-08 Bayer Ag Benzoxazolyl- und Benzothiazolyloxazolidinone
HRP960159A2 (en) 1995-04-21 1997-08-31 Bayer Ag Benzocyclopentane oxazolidinones containing heteroatoms
US5643935A (en) 1995-06-07 1997-07-01 The University Of North Carolina At Chapel Hill Method of combatting infectious diseases using dicationic bis-benzimidazoles
TW538046B (en) 1998-01-08 2003-06-21 Hoechst Marion Roussel Inc Aromatic amides having antiobiotic activities and the preparation processes, intermediates and pharmaceutical composition thereof
AUPP873799A0 (en) 1999-02-17 1999-03-11 Fujisawa Pharmaceutical Co., Ltd. Pyridine compounds
US6156373A (en) 1999-05-03 2000-12-05 Scimed Life Systems, Inc. Medical device coating methods and devices
GB9911594D0 (en) 1999-05-19 1999-07-21 Smithkline Beecham Plc Novel compounds
GB9912413D0 (en) 1999-05-28 1999-07-28 Pfizer Ltd Compounds useful in therapy
US6258121B1 (en) 1999-07-02 2001-07-10 Scimed Life Systems, Inc. Stent coating
US7419678B2 (en) 2000-05-12 2008-09-02 Cordis Corporation Coated medical devices for the prevention and treatment of vascular disease
US20040018228A1 (en) 2000-11-06 2004-01-29 Afmedica, Inc. Compositions and methods for reducing scar tissue formation
BR0116216A (pt) 2000-12-15 2004-08-17 Vertex Pharma Inibidores de girase e seus usos
US20030229390A1 (en) 2001-09-17 2003-12-11 Control Delivery Systems, Inc. On-stent delivery of pyrimidines and purine analogs
PL374315A1 (en) 2001-10-25 2005-10-03 Wisconsin Alumni Research Foundation Vascular stent or graft coated or impregnated with protein tyrosine kinase inhibitors and method of using same
US6939376B2 (en) 2001-11-05 2005-09-06 Sun Biomedical, Ltd. Drug-delivery endovascular stent and method for treating restenosis
US20030204168A1 (en) 2002-04-30 2003-10-30 Gjalt Bosma Coated vascular devices
CA2489128C (en) 2002-06-13 2012-01-03 Vertex Pharmaceuticals Incorporated 2-ureido-6-heteroaryl-3h-benzoimidazole-4-carboxylic acid derivatives and related compounds as gyrase and/or topoisomerase iv inhibitors for the treatment of bacterial infections
US7569591B2 (en) 2003-01-31 2009-08-04 Vertex Pharmaceuticals Incorporated Gyrase inhibitors and uses thereof
US7618974B2 (en) * 2003-01-31 2009-11-17 Vertex Pharmaceuticals Incorporated Gyrase inhibitors and uses thereof
US8404852B2 (en) 2003-01-31 2013-03-26 Vertex Pharmaceuticals Incorporated Gyrase inhibitors and uses thereof
US8193352B2 (en) 2003-01-31 2012-06-05 Vertex Pharmaceuticals Incorporated Gyrase inhibitors and uses thereof
AR042956A1 (es) 2003-01-31 2005-07-13 Vertex Pharma Inhibidores de girasa y usos de los mismos
US7582641B2 (en) 2003-01-31 2009-09-01 Vertex Pharmaceuticals Incorporated Gyrase inhibitors and uses thereof
CN101321744A (zh) * 2005-11-07 2008-12-10 沃泰克斯药物股份有限公司 作为回旋酶抑制剂的苯并咪唑衍生物
GB0612428D0 (en) 2006-06-22 2006-08-02 Prolysis Ltd Antibacterial agents
GB0724349D0 (en) 2007-12-13 2008-01-30 Prolysis Ltd Antibacterial agents
US8481544B2 (en) 2006-06-22 2013-07-09 Biota Europe Limited Antibacterial compositions
ES2363178T3 (es) 2006-12-04 2011-07-26 Astrazeneca Ab Compuestos de urea policíclicos antibacterianos.
GB0724342D0 (en) 2007-12-13 2008-01-30 Prolysis Ltd Anitbacterial compositions
CA2725689A1 (en) * 2008-06-04 2009-12-10 Astrazeneca Ab Thiazolo [5,4-b] pyridine and oxazolo [5,4-b] pyridine derivatives as antibacterial agents
WO2009156966A1 (en) 2008-06-25 2009-12-30 Ranbaxy Laboratories Limited Benzothiazoles and aza-analogues thereof use as antibacterial agents
WO2011032050A2 (en) 2009-09-11 2011-03-17 Trius Therapeutics, Inc. Gyrase inhibitors
JP2013508299A (ja) 2009-10-16 2013-03-07 リブ−エックス ファーマシューティカルズ，インコーポレイテッド 抗微生物性化合物および抗微生物性化合物の製造方法および使用方法
WO2012045124A1 (en) 2010-10-08 2012-04-12 Biota Europe Ltd Bacteria topoisomerase ii inhibiting 2-ethylcarbamoylamino-1, 3-benzothiazol-5-yls
BR112013017977A2 (pt) * 2011-01-14 2019-09-24 Vertex Pharma formas sólidas de inibidor de girase (r) 1-etil-3-[5-[2-{1-hidroxi-1-metil-etil}pirimidin-5-il]-7-(tetrai-drofuran-2-il)-1h-benzimidazol-2-il]ureia
CA2824403C (en) * 2011-01-14 2019-09-24 Vertex Pharmaceuticals Incorporated Solid forms of gyrase inhibitor (r)-1-ethyl-3-[6-fluoro-5-[2-(1-hydroxy-1-methyl-ethyl)pyrimidin-5-yl]-7-(tetrahydrofuran-2-yl)-1h-benzimidazol-2-yl]urea
ES2526902T3 (es) * 2011-01-14 2015-01-16 Vertex Pharmaceuticals Incorporated Procesos de producción de inhibidores de la girasa y topoisomerasa IV
TWI546298B (zh) * 2011-01-14 2016-08-21 維泰克斯製藥公司 旋轉酶及拓樸異構酶ｉｖ抑制劑
EP2721026B1 (de) 2011-06-20 2016-03-02 Vertex Pharmaceuticals Incorporated Phosphatester von gyrase und topoisomeraseinhibitoren
EP2828257B1 (de) 2012-03-22 2017-07-26 Biota Europe Ltd Antibakterielle verbindungen
US9572809B2 (en) * 2012-07-18 2017-02-21 Spero Trinem, Inc. Combination therapy to treat Mycobacterium diseases
US9018216B2 (en) * 2012-07-18 2015-04-28 Vertex Pharmaceuticals Incorporated Solid forms of (R)-2-(5-(2-(3-ethylureido)-6-fluoro-7-(tetrahydrofuran-2-yl)-1H-benzo[d]imidazol-5-yl)pyrimidin-2-yl)propan-2-yl dihydrogen phosphate and salts thereof

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KR101941420B1 (ko) 2019-01-23
ES2576298T3 (es) 2016-07-06
US20130157979A1 (en) 2013-06-20
HK1194365A1 (zh) 2014-10-17
TWI554515B (zh) 2016-10-21
EP2721026A1 (de) 2014-04-23
CN103702994B (zh) 2016-03-23
TW201313732A (zh) 2013-04-01
JP5977344B2 (ja) 2016-08-24
WO2012177707A1 (en) 2012-12-27
US9125922B2 (en) 2015-09-08
JP2014520152A (ja) 2014-08-21
KR20140041768A (ko) 2014-04-04

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